福尔马林所致炎性痛后脑内三种COX亚型的变化及不同选择性COX抑制剂的镇痛效应比较(英文)

Changes of three COX isoforms expression after formalin induced inflammatory pain in brain and analgesic effects of different COX inhibitors

目的:比较炎性痛后三种环氧合酶(cyclooxygenase,COX)亚型的表达变化,以及选择性COX抑制剂不同应用方式对炎性痛的镇痛效应。方法:小鼠足底注射福尔马林诱导炎性痛。用放射免疫分析及RTPCR分别评估脑COX1、COX2及COX3在福尔马林注射前、注射后1、12h、1、3、7、14、30、60d的变化。在镇痛效应的比较中,动物被分成5组:对照组、SC组、NS组、IN组及NS+SC组。前4组分别灌胃生理盐水、SC560、NS398和indomethacin。NS+SC组在前一个月接受NS398,后一个月接受SC560。测定各组动物在福尔马林注射前、注射后1、12h、1、3、7、14、30、60d的热痛阈。结果:COX2的表达在炎性痛后12h到3d升高显著,而COX1的表达在2周到2月升高显著。在整个观察时限内COX3的表达无明显变化。与其他组相比,NS+SC组动物的热痛阈在整个炎性痛过程中均明显提高。结论:炎性痛后早期COX2升高而晚期COX1升高。COX3变化不明显。COX1抑制剂和COX2抑制剂的结合使用比单纯使用其中一种能取得更好的镇痛效果。

AIM: To compare the expression of three cyclooxygenase (COX) isoforms in the process of inflammatory pain and evaluate the analgesic effects of different protocols about usage of COX inhibitors on inflammatory pain. METHODS: Formalin was injected subplantarly to mice to induce inflammatory pain. The expression of COX-1, COX-2 and COX-3 was evaluated by radioimmunoassay and RT-PCR, respectively. For the analgesic effect assay, animals were divided into 5 groups including control, SC, NS, IN and NS+SC group. The former 4 groups received saline, SC-560 (300 (μg·kg^(-1))), NS-398(150 (μg·kg^(-1))), and indomethacin (300 (μg·kg^(-1))) ,respectively. In the NS+SC group, animals received NS-398 during the first 1 month and SC-560 during the second month in the NS+SC group. RESULTS: The expression of COX-1 was higher at the late phase while that of COX-2 was higher at the early phase of inflammatory pain. The expression of COX-3 did not significantly change in the process of inflammatory pain. Additionally, behavioral assessment showed that using COX-2 inhibitors at the early phase followed by COX-1 inhibitors at the late phase could get better analgesic effect on inflammatory pain compared with single using COX-1 selective or COX-2 selective inhibitors. CONCLUSION: In brain, the expression of COX-2 increases rapidly in the inflammatory pain process while COX-1 expression does not increase till the late phase. Brain COX-3 is poorly involved in the inflammatory process. Combined use of COX-1 and COX-2 selective inhibitors may be a better protocol in inflammatory pain treatment.